Non-melanoma skin cancer is the most common form of cancer worldwide. We previously documented an anti-apoptotic role for CDC25A in cutaneous squamous cell carcinoma (SCC), an activity dependent on its association with 14-3-3 proteins. We hypothesized that targeting CDC25A-14-3-3ε interactions may be an effective strategy for inducing skin cancer cell apoptosis. Co-immunoprecipitation revealed that CDC25A associated with 14-3-3ε, 14-3-3γ and 14-3-3ζ in SCC cells but not normal keratinocytes. 14-3-3ε and CDC25A activated Akt/BAD/Survivin pro-survival signaling. To target the interaction of 14-3-3ε with CDC25A for cancer therapy, we developed two novel phospho-peptides, pS and pT, corresponding to each of the 14-3-3 binding sites of CDC25A, to specifically interfere with 14-3-3ε binding to CDC25A. Peptides pT (IC 50 = 22.1 μM), and pS (IC 50 = 29 μM) induced SCC cell death and blocked 14-3-3ε binding to CDC25A. pS or pT treatment of SCC xenografts increased apoptotic cell death and decreased pro-survival P-Akt (S473) and Survivin, demonstrating the effectiveness of the peptides in vivo. These findings lay a framework for the further development of peptides to target 14-3-3ε-CDC25A interactions for skin cancer treatment.

More than a million cases of cutaneous squamous cell carcinoma (SCC) are diagnosed in the U.S.A. each year and its incidence is increasing. Most of these malignancies arise from premalignant lesions, providing an opportunity for intervention before malignant progression. We previously documented how cytoplasmic mislocalization of CDC25A in premalignant and malignant skin cancers confers resistance to apoptotic cell death via a mechanism that depends on its interaction with 14-3-3ε. From these data, we hypothesized that 14-3-3ε over-expression drives skin tumor development and progression, such that targeting 14-3-3ε may be a useful strategy for skin cancer treatment. Like CDC25A, 14-3-3ε was overexpressed and mislocalized to the cytoplasm of both benign and malignant human skin cancer. Skin-targeted deletion of the 14-3-3ε gene reduced skin tumor development by 75% and blocked malignant progression. 14-3-3ε suppressed apoptosis through activation of Akt, leading to inhibition of BAD and up-regulation of Survivin. Using virtual tetrapeptide libraries, we developed a novel peptide that specifically blocked 14-3-3ε heterodimerization, and thereby prevented its interaction with CDC25A. The peptide reduced pro-survival signaling, killed skin cancer cells, and reduced skin tumor growth in xenograft. Normal skin keratinocytes were unaffected by inhibition or deletion of 14-3-3ε. Thus, targeting of 14-3-3ε dimerization is a promising strategy for treatment of premalignant skin lesions.

Vibrio vulnificus is an opportunistic marine pathogen that can cause fatal septicemic disease in both humans and eels (Gulig, Bourdage, & Starks, 2005;Morris, 1988). Human infections are generally associated with eating contaminated seafood or through open wounds that are exposed to contaminated seawater (Linkous & Oliver, 1999;Strom & Paranjpye, 2000). Fatal primary septicemia can progress rapidly, resulting in a mortality rate of >50% within days. In humans, V. vulnificus preferentially infects those who have pre-existing conditions associated with elevated iron levels, including cirrhosis, hemochromatosis, and thalassemia (Gulig et al., 2005).Vibrio vulnificus strains are divided into three biotypes: 1, 2, and 3. Biotypes 1 and 3 are known as opportunistic pathogens in humans while the Biotype 2 is primarily an eel pathogen, and only particular isolates have been implicated in human infection (

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Basal cell carcinoma (BCC) is a highly prevalent epidermal neoplasm that most commonly occurs in regions of sun-exposed skin, though rare cases arise in sun-protected areas. BCCs of the vulva account for a small fraction of cases and can be mistaken for other cutaneous genital pathologies on clinical examination. Here we report a case of vulvar BCC that presented as a firm, tender bilateral lesion of the mons pubis and was diagnosed by histopathology and immunostaining for classical BCC markers.